Preliminary studies in this laboratory demonstrated that the character of the adrenergic receptor system of the rat liver changes as the animal matures. These changes which were assessed from studies of the influence of various adrenergic agonists and antagonists on carbohydrate metabolism in isolated rat hepatocytes indicate that functional alpha-adrenergic receptors are lost as the rat matures. Furthermore, in fully mature adults the alpha-adrenergic receptor system appears to become coupled to adenylate cyclase, an unusual observation. Our particular interest is that loss of functional beta-adrenergic receptors appears to result in a loss of capacity for epinephrine to modulate pyruvate kinase activity and glycolytic flux in the rat hepatocyte. The purpose of the proposed investigation is to undertake further investigation of the changes in the adrenergic receptor system which occurs as the rat developes and ages. Our past studies with juvenile and young adult rats will be expanded to examine weanling and aged rats. Also experimental measurements will be expanded to examine more directly the adrenergic receptors using specific radioligands developed for that purpose. And direct measurements of catecholamine-stimulated adenylate cyclase activity will be carried out using hepatocyte homogenates to determine if alpha-adrenergic receptors become directly coupled to adenylate cyclase in old rats. Reports from other laboratories indicate that certain physiological and pathological conditions also are associated with changes in the nature of the adrenergic control of liver metabolism and we will also investigate these conditions which include: diabetes, adrenalectomy, and hypothroidism. Finally, limited studies will also be undertaken with hepatocytes from rabbits and guinea pigs to determine if the age related changes in adrenergic control of liver carbohydrate metabolism is of general importance to species other than the rat.